DXA evaluation of bone fragility 2 years after bariatric surgery in patients with obesity

Purpose The primary objective was to evaluate bone fragility on dual X-ray absorptiometry (DXA) in patients with obesity before and 2 years after bariatric surgery. The secondary objective was to identify risk factors for the development of a bone mineral density ≤ −2 SD at 2 years. Methods This descriptive study included patients with obesity who underwent DXA before and 2 years (±6 months) after bariatric surgery. The BMD and the T-score were assessed at the lumbar spine, femoral neck and total hip. Data on body composition on DXA were also collected. The diagnosis of osteoporosis was retained for a T-score ≤ − 2.5 SD at any measured location. Osteopenia, or low bone mass, was defined by −2.5 SD < T-score ≤ −1 SD. Results Among the 675 included patients, 77.8 % were women, with a mean age of 49.5 years (±11.1). After bariatric surgery, there were significantly more patients with osteoporosis: 3.6 % vs. 0.9 % (p = 0.0001). Multivariate analysis revealed that the risk factors for developing a bone mineral density ≤ −2 SD 2 years after bariatric surgery in patients with normal BMD before surgery were age and lower lean and fat mass before the surgery (OR = 1.07, 95%CI = [1.03–1.12], OR = 0.83, 95%CI = [0.77–0.91], OR = 1.08, 95%CI = [1.02–1.15], respectively). Conclusion There was a significantly higher prevalence of osteoporosis and low bone mass 2 years after bariatric surgery. Older age and lower lean and fat mass at baseline were risk factors for the development of a BMD ≤ -2SD at 2 years.


Introduction
Obesity and osteoporosis have become major global health problems due to their increasing prevalence (Sarafrazi, 2021;Apovian, 2016).The interaction between these two diseases is complex and not fully understood.
Osteoporosis is a disease characterized by a decrease in bone mass and deterioration of bone microarchitecture leading to fragility fractures (Lane et al., 2000).The gold standard for osteoporosis diagnosis is dual X-ray absorptiometry (DXA) (Dimai, 2017).
Bariatric surgery is recognized as a highly effective therapy for obesity, allowing weight loss, a reduction in comorbidities and mortality, and an improvement in quality of life (Borisenko et al., 2015;Lupoli et al., 2017).In the literature, obesity seems to be a protective factor for bone (Murray et al., 2017;Lespessailles et al., 2019a), but some studies have shown a higher risk of fracture in patients with obesity (Gonnelli et al., 2014;Tencerova et al., 2019), probably due to an alteration of the bone architecture, with increased bone marrow adipose tissue (Ambrosi et al., 2017;Boskey and Imbert, 2017;Naveiras et al., 2009).According to many studies, malabsorptive procedures lead to a decrease in bone mineral density and sometimes an increased risk of fragility fractures (Geoffroy et al., 2019;Axelsson et al., 2018;Lespessailles et al., 2019b;Ko et al., 2016;Lu et al., 2015).A reduction in bone mineral density (BMD) and an increase of bone turnover markers was previously described (Hofsø et al., 2020).However, the kinetics of bone loss and its physiopathology are unclear.
In French recommendation, it is recommended to perform routinely an initial assessment of fracture risk ideally before the first bariatric surgery procedure in the case of RYGB and biliopancreatic diversion, and in patients at high risk of fracture, regardless of age, and in all menopausal women and all men ≥50 years old, regardless of the type of bariatric surgical procedure.Anti-osteoporosis treatment is indicated for menopausal women and men ≥50 years old with no history of fracture and a T-score ≤ − 2 (Paccou et al., 2022a).
The primary objective of this study was to evaluate bone fragility on DXA in patients with obesity before and 2 years after bariatric surgery.The secondary objective was to identify risk factors for developing abnormal BMD ≤ − 2 SD at 2 years.

Population
This descriptive study included patients with obesity who underwent bariatric surgery in our specialized obesity center between January 2014 and December 2019.To be included, patients had to have undergone DXA before and two years (±6 months) after bariatric surgery.All exams had to be performed at the same center during routine pre-and postoperative follow-up visits.The exclusion criteria were gastric banding and ring ablation.Demographic and anthropometric data (age, sex, smoking and alcohol consumption habits, body height and weight to calculate BMI) and comorbidities such as diabetes and cardiovascular risk factors (dyslipidemia, hypertension) were collected from complete medical records.To evaluate osteoporosis, clinical risk factors (sex, age, smoking and alcohol consumption habits) and vitamin D status were also collected (vitamin D deficiency was defined by a level below 30 ng/ mL).Vitamin D evaluation was performed in the same laboratory with chemiluminescence immunoassay (Diasorin).

DXA evaluation
Any available pre-and postoperative DXA was used.The preoperative DXA closest to the date of surgery and postoperative DXA performed between 18 and 30 months after surgery (2 years ±6 months) were retained.All DXA was performed on a Lunar Prodigy densitometer (Advance PA +301,010, Encore, version 14.10.022;Madison, WI, 53718, USA).The BMD and the T-score were assessed for each patient at the lumbar spine, femoral neck and total hip.The diagnosis of osteoporosis was retained for a T-score ≤ − 2.5 SD at any measured location.Osteopenia, or low bone mass, was defined by − 2.5 SD < T-score ≤ − 1 SD (World Health Organ. Tech. Rep. Ser., 1994).Data on lean and fat mass and their distribution (arms, legs, trunk, android vs. gynoid fat and lean mass and visceral fat mass) were also collected from DXA whole body examination (limbs included).

Ethics approval
All of the data used were obtained from medical records.No examinations were performed to determine if the patients met the inclusion criteria.This study is registered with the Information Technology and Freedoms Commission for our University Hospital and on Clinicaltrials.gov (file number: 2019PI216) and was designed in accordance with the general ethical principles outlined in the Declaration of Helsinki.The protocol of this study was approved by the Information Technology and Freedoms Commission for our University Hospital.All patients gave their consent for the use of their medical data from the time period they received medical care at the University Hospital.

Statistical analysis
Both descriptive and comparative analyses were conducted by accounting for the nature and distribution of the variables.Qualitative variables are described as frequencies and percentages; quantitative variables are reported as the mean ± SD or as the median and interquartile range (IQR).The Kolmogorov-Smirnov test showed that among the continuous demographic and clinical variables, only age, height, and weight followed a normal distribution.
For comparisons of the data before and two years after surgery, a paired Student's t-test and Chi-squared test were used for variables with a normal distribution, and the Wilcoxon signed rank test and Mann-Whitney U test were used for other continuous variables.For qualitative variables, the McNemar test was used, and logistic regression was performed to identify the variables significantly associated with the appearance of a T-score ≤ − 2 SD.Significant results (univariate and multivariate analysis) are presented with their p values, odds ratio (OR) and 95 % confidence interval (95%CI).The significance level was set at 0.05 for the entire study.IBM SPSS Statistics v23 was used for data analysis.

Population
In total, 675 patients underwent DXA before and two years (±6 months) after bariatric surgery.The characteristics of the patients are described in Table 1.
At baseline, before bariatric surgery, the mean age of the patients was 49.5 years (±11.1),77.8 % were women, the mean weight was 124.9 kg (±22.4), and the mean BMI was 45.3 kg/m 2 (±6.5); 30.7 % of patients had diabetes, and 60.1 % had cardiovascular risk factors.In total, 38.2 % of the patients used tobacco, and 3.6 % consumed alcohol; 83 % of the patients presented vitamin D deficiency.

Patient characteristics two years after surgery
Two years after bariatric surgery, the mean weight was 82.6 kg (±18.6), and the mean BMI was 29.9 kg/m 2 (±5.7).The mean weight change was 42.3 kg (±15.1).The change in BMI was statistically significant (p = 0.0001).
There were more patients with osteoporosis or low bone mass (at the femoral neck, hip and spine): 6 patients (0.9 %) had osteoporosis in at least one site before surgery, and 24 (3.6 %) had osteoporosis two years after surgery.This difference was statistically significant (p = 0.0001).Their T-score and BMD were significantly lower after bariatric surgery (p = 0.0001 for each).
The patients' characteristics at 2 years and the comparison with baseline characteristics are described in Table 2.

Risk factors for the appearance of a BMD ≤ − 2 SD on at least one site at 2 years after bariatric surgery
Before surgery, 618 patients (91.6 %) presented a normal DXA result (T-score > − 2 SD).Two years after the surgery, 44 of them (7.1 %) presented a T-score ≤ − 2 SD (Table 3).
For these patients, in the univariate analysis (Table 3), the risk factors for having a T-score ≤ − 2 SD at two years were an older age (p = 0.0001), a lower weight before and after the surgery (p = 0.022 and 0.0001, respectively), a lower BMI after surgery (p = 0.01), a lower lean and fat mass before surgery (p = 0.033 and 0.0001, respectively) and a lower appendicular lean mass adjusted to height (p = 0.0001).

Discussion
In this study, a large cohort of patients, with a large predominance of women and a mean age under 50 years, who underwent bariatric surgery, representative of patients with obesity (Kanter and Caballero, 2012;Hales et al., 2020), was evaluated.The mean reduction of BMI was consistent with the data in the literature, with a BMI reduction between 13.2 and 16 kg/m 2 after sleeve gastrectomy or GBP (Silva et al., 2019;Junquera Bañares et al., 2021).Because the amount of weight lost peaked at the 2-year follow-up and was relatively stable after this time point (O'Brien et al., 2019), studies at 2 years may be interesting in view of the weight stabilization observed.Gastric bypass (GBP) represented The statistically significant difference in the osteoporosis and low bone mass prevalence before and 2 years after bariatric surgery and Tscore and BMD significantly lower after bariatric surgery at any site were in accordance with the literature.Previous studies have shown a decrease in BMD at the femoral neck, spine and hip (Ko et al., 2016;Paccou et al., 2022b;Krez and Stein, 2020;Jammah, 2015;von Mach et al., 2004;Pugnale et al., 2003;Mele et al., 2022).Ko et al. performed a meta-analysis (Ko et al., 2016) showing that BMD at the femoral neck decreased after bariatric surgery compared to that in nonsurgical controls, whereas BMD at the lumbar spine did not show a difference between the two groups.Bone loss following bariatric surgery is multifactorial (Krez and Stein, 2020;Mele et al., 2022), including highturnover bone loss (Paccou et al., 2022b) and an alteration of the bone architecture with increased bone marrow adipose tissue (Ambrosi et al., 2017;Boskey and Imbert, 2017;Naveiras et al., 2009).Metabolic bone disease is due to complex interactions between signaling factors in the gut, bone, and fat tissues (Jammah, 2015).Furthermore, malabsorptive surgical techniques (sleeve gastrectomy, gastric bypass) create digestive malabsorption of calcium, vitamin D, and other nutrients (Jammah, 2015).Current management should be geared toward bone loss prevention and nutritional deficiency correction.Pharmacological treatments should be considered for high-risk patients or patients with fractures without traumatism.The percentage of bone loss is strongly correlated with the speed of weight loss (Jammah, 2015).
We found no relationship between weight loss and DXA changes after surgery.This is probably due to the low kinetics of bone modifications.
In multivariate analysis, the risk factors for the development of Tscore ≤ − 2 SD) at 2 years were age and lower lean and fat mass before surgery.These results were consistent with those in the literature for age (Kelsey, 1989).Concerning lean mass, our result is consistent with the literature.An involuntary loss of skeletal muscle mass was previously positively correlated with bone density and the development of fragility fractures (Hida et al., 2016;Sipilä et al., 2020), but no threshold of lean mass loss was previously described.
Our study has some limitations.Most of the bariatric surgery interventions involved GBP (91.7 %), so restrictive procedures were not evaluated.The retrospective modality did not permit us to explore the fracture events, to have more information about menopausal status, presence of endocrine diseases.We also have no specific data on medicine-related bone illness and specific treatment for osteoporosis.After surgery, all patients have a vitamin D supplementation and a calcium supplementation in case of high parathyroid hormone level and/or low calciuria and/or calcium intake <900 mg/day.DXA remains the gold standard to diagnose osteoporosis, but it is known that BMD increases with BMI (Scibora et al., 2012) and that photon penetration is reduced through soft tissues (Yu, 2014), which is why mass variation during the follow-up could have influenced the DXA values, with an underestimation of bone fragility for patients with elevated fat mass.
In a previous study (Halin et al., 2022), we found similar results with a CT osteoporosis study.There was a higher prevalence of bone fragility 2 years after bariatric surgery than before.Unfortunately, the populations of these 2 studies were similar but not identical, and thus we cannot compare the 2 modalities of osteoporosis screening.The correlation between CT and DXA, which was previously studied in patients with obesity, is positive but poor (Halin et al., 2022).This lack of relationship could be explained by the difference in measurements between the 2 exams.CT excludes cortical bone, is less influenced by body fat mass and is more representative of real bone mass than DXA (Halin et al., 2022).In the literature, Yu et al. also found discordant results between DXA and QCT bone density (Yu et al., 2014).
In conclusion, there is a higher prevalence of osteoporosis and low bone mass after bariatric surgery, and these results should encourage practitioners to perform bone screening before and after this surgery to diagnose osteoporosis before fracture involvement, according to the recommendations (Paccou et al., 2022a;Mechanick et al., 2013), especially in older patients with a lower lean and fat mass at baseline.All of the risk factors for development of a BMD ≤ − 2 SD at 2 years (indication of anti-osteoporosis treatment for menopausal women and men ≥50 years old) were preoperative characteristics.Longitudinal follow-up may be warranted to precisely determine the kinetics of bone loss after bariatric surgery and to establish thresholds for screening or therapeutic interventions.Data are presented as the mean (SD) for continuous demographic variables with a normal distribution and the median [interquartile range] for those with a nonnormal distribution.Logistic regression was performed to identify the variables significantly associated with the binary outcome of T-score ≤ − 2 SD.The results in bold are statistically significant (p < 0.05).

Table 1
Characteristics of the patients at baseline (n = 675).

Table 2
Comparison of the included patients' characteristics before and at 2 years after bariatric surgery (n = 675).
Data are presented as n (%) for dichotomous variables, the mean (SD) for continuous demographic variables with a normal distribution and the median [interquartile range] for those with a nonnormal distribution.The percentage was calculated based on the available data for each variable.ALM/H 2 : appendicular lean mass adjusted to height; ALM/W: appendicular lean mass adjusted to body weight; BMD: bone mineral density; BMI: body mass index; DXA: dual-energy X-ray absorptiometry; GBP: gastric bypass; VAT: visceral adipose tissue.Osteoporosis was defined by a T-score ≤ − 2.5 SD at any measured location, and low bone mass was defined by − 2.5 SD < T-score ≤ − 1 SD.Vitamin D deficiency was defined by a level below 30 ng/mL.The results in bold are statistically significant (p < 0.05).For comparisons of the data before and two years after surgery, a paired Student's t-test was used for variables with a normal distribution, and the Wilcoxon signed rank test was used for other continuous variables.For qualitative variables, the McNemar test was used.

Table 3
Characteristics at 2 years of the patients with a normal DXA (T-score > − 2 SD) at baseline (before bariatric surgery) (n = 618).Data are presented as n (%) for dichotomous variables, the mean (SD) for continuous demographic variables with a normal distribution and the median [interquartile range] for those with a nonnormal distribution.The percentage was calculated based on the available data for each variable.ALM/H 2 : appendicular lean mass adjusted to height; BMD: bone mineral density; BMI: body mass index; DXA: dual-energy X-ray absorptiometry; GBP: gastric bypass; VAT: visceral adipose tissue.Vitamin D deficiency was defined by a level below 30 ng/mL.p value: a Mann-Whitney U test for variables with nonnormal distribution and Chi-squared for variables with normal distribution and logistic regression were performed to identify the variables significantly associated with the binary outcome of T-score ≤ − 2 SD.The results in bold are statistically significant (p < 0.05).Univariate and multivariate analysis results (Threshold ≤ − 2 SD).